Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells.

2.50
Hdl Handle:
http://hdl.handle.net/2436/15800
Title:
Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells.
Authors:
Foreman, Megan A.; Gu, Yuchun; Howl, John D.; Jones, Sarah; Publicover, Stephen J.
Abstract:
Nitric oxide (NO) is pivotal to bone physiology. In the central nervous system constitutive, Ca(2+)-calmodulin regulated NO synthase activity and glutamate signalling are intimately linked. Since L-glutamate signalling occurs in bone and is implicated in bone regulation, we have investigated the effect of L-glutamate on NO synthase in bone-derived cells. Treatment of marrow stromal cells with L-glutamate reduced basal NO synthase activity by 40%. Imaging showed that L-glutamate caused a rapid, usually localised and slowly-reversible fall in [Ca(2+)](i). This effect was resistant to disruption of intracellular Ca(2+) stores but sensitive to extracellular La(3+) or omission of extracellular Ca(2+), demonstrating that glutamate acts by inhibition of membrane Ca(2+) influx. The only previous description of such an effect of L-glutamate is via activation of the group III receptor, mGluR6, in the retina. Using Western blotting and RT-PCR we detected mGluR6 protein and transcripts in marrow stromal cells. The effects of L-glutamate on NOS activity and [Ca(2+)](i) in marrow stromal cells were abolished by a group III mGluR inhibitor, (S)-2-amino-2-methyl-4-phosphonobutyric acid. Recording of membrane potential showed that, similarly to the effects of retinal mGluR6 activation, L-glutamate induced membrane hyperpolarisation (-16 +/- 2 mV), which was also sensitive to group III mGluR inhibition. L-glutamate had no effect on cAMP levels. We conclude that activation of a group III mGluR in bone marrow stromal cells inhibits a Ca(2+)-permeable plasma membrane channel, reducing [Ca(2+)](i) and suppressing generation of NO. These observations directly link bone L-glutamate signalling to processes central to bone growth and regulation.
Citation:
Journal of Cellular Physiology, 204(2): 704-713
Publisher:
Wiley InterScience
Issue Date:
2005
URI:
http://hdl.handle.net/2436/15800
DOI:
10.1002/jcp.20353
PubMed ID:
15799084
Additional Links:
http://www3.interscience.wiley.com/journal/110433685/abstract
Type:
Article
Language:
en
Description:
Metadata only
ISSN:
0021-9541
Appears in Collections:
Molecular Pharmacology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorForeman, Megan A.-
dc.contributor.authorGu, Yuchun-
dc.contributor.authorHowl, John D.-
dc.contributor.authorJones, Sarah-
dc.contributor.authorPublicover, Stephen J.-
dc.date.accessioned2008-01-08T10:43:39Z-
dc.date.available2008-01-08T10:43:39Z-
dc.date.issued2005-
dc.identifier.citationJournal of Cellular Physiology, 204(2): 704-713en
dc.identifier.issn0021-9541-
dc.identifier.pmid15799084-
dc.identifier.doi10.1002/jcp.20353-
dc.identifier.urihttp://hdl.handle.net/2436/15800-
dc.descriptionMetadata onlyen
dc.description.abstractNitric oxide (NO) is pivotal to bone physiology. In the central nervous system constitutive, Ca(2+)-calmodulin regulated NO synthase activity and glutamate signalling are intimately linked. Since L-glutamate signalling occurs in bone and is implicated in bone regulation, we have investigated the effect of L-glutamate on NO synthase in bone-derived cells. Treatment of marrow stromal cells with L-glutamate reduced basal NO synthase activity by 40%. Imaging showed that L-glutamate caused a rapid, usually localised and slowly-reversible fall in [Ca(2+)](i). This effect was resistant to disruption of intracellular Ca(2+) stores but sensitive to extracellular La(3+) or omission of extracellular Ca(2+), demonstrating that glutamate acts by inhibition of membrane Ca(2+) influx. The only previous description of such an effect of L-glutamate is via activation of the group III receptor, mGluR6, in the retina. Using Western blotting and RT-PCR we detected mGluR6 protein and transcripts in marrow stromal cells. The effects of L-glutamate on NOS activity and [Ca(2+)](i) in marrow stromal cells were abolished by a group III mGluR inhibitor, (S)-2-amino-2-methyl-4-phosphonobutyric acid. Recording of membrane potential showed that, similarly to the effects of retinal mGluR6 activation, L-glutamate induced membrane hyperpolarisation (-16 +/- 2 mV), which was also sensitive to group III mGluR inhibition. L-glutamate had no effect on cAMP levels. We conclude that activation of a group III mGluR in bone marrow stromal cells inhibits a Ca(2+)-permeable plasma membrane channel, reducing [Ca(2+)](i) and suppressing generation of NO. These observations directly link bone L-glutamate signalling to processes central to bone growth and regulation.en
dc.language.isoenen
dc.publisherWiley InterScienceen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/110433685/abstracten
dc.subjectNitric oxideen
dc.subjectBone physiologyen
dc.subjectBone marrow stromal cellsen
dc.subjectGlutamate signallingen
dc.titleGroup III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells.en
dc.typeArticleen
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